Effect of inhibitors of arachidonic acid metabolism on alpha-aminoisobutyric acid transport in human lymphocytes.
The role of arachidonic acid metabolism (or metabolites) in the modulation of alpha-aminoisobutyric acid transport in resting and concanavalin A-stimulated human peripheral blood lymphocytes was evaluated using previously characterized inhibitors of arachidonic acid metabolism. Nordihydroguairetic acid (a nonselective antioxidant), 5,8,11,14-eicosatetraynoic acid (an inhibitor of lipoxygenase and cyclooxygenase activities), indomethacin and acetylsalicylic acid (selective cyclooxygenase inhibitors), and 1-benzylimidazole, Ro-22-3581 and Ro-22-3582 (thromboxane synthetase inhibitors) proved to be potent inhibitors of amino acid transport activity in normal resting and lectin-activated lymphocytes at concentrations known to decrease thromboxane A2 production. The rank order of effectiveness of these various inhibitors compared favorably with their relative potencies as inhibitors of thromboxane B2 synthesis under the same conditions, as determined by radioimmunoassay. Inhibitory effects noted were not due to overt cytotoxicity and seemed to involve changes primarily in the Vmax and not the Km of the transport process. Drug-induced alterations in the magnitude of concanavalin A binding were not observed. These results suggest that the activity of amino acid transport systems can be influenced by certain arachidonic acid metabolites, probably thromboxanes, in both stimulated and unstimulated lymphocytes. In addition, these findings may provide a partial explanation for the observation that inhibitors of thromboxane formation prevent lymphocyte mitogenesis.
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000480:Alkynes / Q000494:pharmacology; D000621:Aminoisobutyric Acids / Q000097:blood*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood*; D001693:Biological Transport, Active / Q000187:drug effects; D002396:Catechols / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D009637:Masoprocol; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D000480:Alkynes; D000621:Aminoisobutyric Acids; D001095:Arachidonic Acids; D002396:Catechols; D016861:Cyclooxygenase Inhibitors; D015117:5,8,11,14-Eicosatetraynoic Acid; D016718:Arachidonic Acid; D009637:Masoprocol; D013930:Thromboxane-A Synthase